How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group.

PURPOSE: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. METHODS: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. RESULTS: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. CONCLUSIONS: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology.

Three-dimensional, high-definition exoscopic parotidectomy: a valid alternative to magnified-assisted surgery.

The authors report their experience regarding parotidectomy performed under a three-dimensional-high-definition (3D-HD) exoscope, with the aim of evaluating its effectiveness in parotid surgery. This is a prospective study on nine patients treated by the same surgeon. All patients underwent parotidectomy for extrafacial primary tumours without preoperative involvement of the skin or of the facial nerve from March 2019 to June 2019 with the use of a 3D-HD exoscope. Magnification was variable from 8x to 30x with direct vision supplied by a 3D monitor. Six men and three women, mean (range) age 47.8 (19-74) years underwent parotidectomy. No patient experienced postoperative complications or definitive facial palsy. The mean (range) time of surgery was 149.4 (115 - 210) minutes. The 3D exoscope represents a valid alternative to the operative microscope or surgical loupe for parotid surgery. It is a light instrument allowing for precise surgical dissection of the parotid region by reducing the risks for iatrogenic lesions of the facial nerve using a real 3D magnification of the anatomical structures in HD. Furthermore, its use does not prolong the operative time and shows high potential for training and educational purposes since the operating room staff can better perceive the procedure and the surgeon's fine gestures. Although the preliminary applications show promising results, there is still a need for wider scientific validation.

Exploring cocoa properties: is theobromine a cognitive modulator?

Nutritional qualities of cocoa have been acknowledged by several authors; a particular focus has been placed on its high content of flavanols, known for their excellent antioxidant properties and subsequent protective effect on cardio- and cerebrovascular systems as well as for neuromodulatory and neuroprotective actions. Other active components of cocoa are methylxanthines (caffeine and theobromine). Whereas the effects of caffeine are extensively researched, the same is not the case for theobromine; this review summarizes evidence on the effect of theobromine on cognitive functions. Considering animal studies, it can be asserted that acute exposition to theobromine has a reduced and delayed nootropic effect with respect to caffeine, whereas both animal and human studies suggested a potential neuroprotective action of long-term assumption of theobromine through a reduction of Aß amyloid pathology, which is commonly observed in Alzheimer's disease patients' brains. Hence, the conceivable action of theobromine alone and associated with caffeine or other cocoa constituents on cognitive modulation is yet underexplored and future studies are needed to shed light on this promising molecule.

Clinical Characteristics of Dogs with Progressive Myelomalacia Following Acute Intervertebral Disc Extrusion.

BACKGROUND: Progressive myelomalacia (PMM) is a catastrophic disease associated with acute intervertebral disc extrusion (IVDE). Published data on the clinical characteristics of this disease are limited. OBJECTIVE: To describe the onset and progression of clinical signs of PMM in a large case cohort. ANIMALS: Fifty-one dogs, 18 with histopathologically confirmed PMM, 33 presumptively diagnosed based on clinical signs and diagnostic imaging. METHODS: Retrospective study. Dogs with confirmed IVDE and either a histopathologic diagnosis of PMM or a high clinical suspicion were identified by medical record search. Data on nature and progression of signs were extracted. RESULTS: Twenty-four of 51 dogs were Dachshunds. T12-T13 was the most common site of disc extrusion (12 of 56), and 18 of 55 of mid-to-caudal lumbar discs (between L3 and L6) were affected. Onset of PMM signs ranged from present at first evaluation (17/51) to 5 days after presentation, with 25 of 51 cases developing signs within 48 hours. Progression of signs from onset of PMM to euthanasia or death, excluding 7 cases euthanized at presentation, ranged from 1 to 13 days with 23 being euthanized within 3 days. Nonspecific systemic signs were documented in 30 of 51 dogs. CONCLUSION AND CLINICAL IMPORTANCE: The majority of dogs developed PMM within 2 days of presentation and was euthanized within another 3 days. However, onset can be delayed up to 5 days after presentation with progression to euthanasia taking as long as 2 weeks. Mid-to-caudal lumbar discs might be associated with an increased risk of PMM.

Associations Between Anesthetic Variables and Functional Outcome in Dogs With Thoracolumbar Intervertebral Disk Extrusion Undergoing Decompressive Hemilaminectomy.

BACKGROUND: Outcome of acute experimental spinal cord injury is strongly associated with tissue perfusion and oxygenation. Cardiopulmonary depression could affect outcome in dogs undergoing general anesthesia for surgical treatment of thoracolumbar intervertebral disk extrusion (IVDE). HYPOTHESIS/OBJECTIVES: To evaluate the effects of general anesthesia on functional outcome in dogs undergoing surgery to treat thoracolumbar IVDE. ANIMALS: Eighty-four client-owned dogs with acute thoracolumbar IVDE treated by decompressive hemilaminectomy. METHODS: Exploratory, retrospective observational study. Medical records were reviewed for clinical presentation and anesthetic monitoring variables, including duration of anesthesia and surgery, hypotension, bradycardia, temperature, and respiratory parameters. Multivariable regression tree analysis was performed to explore associations between anesthetic variables and functional outcome scores after 6 weeks, as well as return to ambulatory status. RESULTS: Episodes of bradycardia (69%) and hypotension (57%) were frequent. Across all outcome measures, regression tree analysis highlighted functional grade at presentation as the primary determining factor, and among pain perception negative dogs, there was a possible association between increased duration of surgery and poorer outcome. In dogs with intact pain perception, duration of bradycardia, mean body temperature, and mean end-tidal carbon dioxide were highlighted. CONCLUSIONS AND CLINICAL IMPORTANCE: Exploratory statistical methods can facilitate hypothesis-generating studies to inform prospective investigations in veterinary medicine. Although the mechanism is uncertain, increased duration of surgery might be associated with poorer outcome in pain perception negative dogs with thoracolumbar IVDE.

A Placebo-Controlled, Prospective, Randomized Clinical Trial of Polyethylene Glycol and Methylprednisolone Sodium Succinate in Dogs with Intervertebral Disk Herniation.

BACKGROUND: Acute intervertebral disk herniation (IVDH) is a common cause of spinal cord injury in dogs and currently there is no proven medical treatment to counter secondary injury effects. Use of methylprednisolone sodium succinate (MPSS) or polyethylene glycol (PEG) as neuroprotectants is advocated but controversial because neither treatment has been tested in placebo-controlled, randomized, blinded trials in dogs. HYPOTHESIS: Polyethylene glycol will improve the outcome of severe spinal cord injury caused by IVDH compared to MPSS or placebo. ANIMALS: Client-owned dogs with acute onset of thoracolumbar IVDH causing paralysis and loss of nociception for <24 hours. METHODS: Dogs were randomized to receive MPSS, PEG, or placebo; drugs appeared identical and group allocation was masked. Drug administration was initiated once the diagnosis of IVDH was confirmed and all dogs underwent hemilaminectomy. Neurologic function was assessed 2, 4, 8, and 12 weeks postoperatively using an open field gait score (OFS) as the primary outcome measure. Outcomes were compared by the Wilcoxon rank sum test. RESULTS: Sixty-three dogs were recruited and 47.6% recovered ambulation. 17.5% developed progressive myelomalacia but there was no association with group. There was no difference in OFS among groups. Although full study power was not reached, conditional power analyses indicated the futility of continued case recruitment. CONCLUSIONS: This clinical trial did not show a benefit of either MPSS or PEG in the treatment of acute, severe thoracolumbar IVDH when used as adjunctive medical treatment administered to dogs presenting within 24 hours of onset of paralysis.

Histiocytic sarcoma with central nervous system involvement in dogs: 19 cases (2006-2012).

BACKGROUND: Reports of histiocytic sarcoma (HS) involving the central nervous system (CNS) are sparse and consist mainly of case reports describing 1-3 animals. OBJECTIVE: The objective of this study was to report the signalments, clinical signs, clinicopathologic and diagnostic imaging findings, treatment, and outcome of a series of dogs with HS and CNS involvement. ANIMALS: Nineteen dogs with HS examined at veterinary referral hospitals. METHODS: Retrospective case series. Medical records were reviewed and cases with a histopathological diagnosis of CNS HS were included in the study. Diagnostic imaging studies of the CNS were evaluated and histopathologic samples were reviewed to confirm the diagnosis. RESULTS: Retrievers and Pembroke Welsh Corgis were overrepresented in this cohort of dogs. Tumors involved the brain in 14 dogs and the spinal cord in 5. In 4 dogs, HS was part of a disseminated, multiorgan process whereas it appeared confined to the CNS in 15 dogs. Diagnostic imaging had variable appearances although extraaxial masses predominated in the brain. There was meningeal enhancement in all dogs that was often profound and remote from the primary mass lesion. Pleocytosis was present in all dogs with CSF evaluation. Median survival was 3 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Breed predispositions appear to vary from reports of HS in other organ systems. Some unique imaging and clinicopathologic characteristics, particularly brain herniation, profound meningeal enhancement, and pleocytosis in combination with 1 or more mass lesions, might help to differentiate this neoplasm from others involving the CNS, although this requires further study.

Frameless stereotactic radiosurgery for the treatment of primary intracranial tumours in dogs.

Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well-defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause-specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy.

Characterization of immune cell infiltration into canine intracranial meningiomas.

Meningiomas are the most common intracranial tumors in dogs. A variety of inflammatory cells have been shown to invade these tumors in people, but little is known about interactions between the immune system and naturally occurring brain tumors in dogs. The purpose of this study was to investigate the presence of a variety of immune cell subsets within canine intracranial meningiomas. Twenty-three formalin-fixed, paraffin-embedded tumor samples were evaluated using immunohistochemistry with antibodies specific for CD3, CD79a, CD18, CD11d (αD), CD45RA, forkhead box P3, and Toll-like receptors 4 and 9. Immune cell infiltration was evident in all samples, with a predominance of CD3(+) T cells. Large numbers of CD18(+) microglia and macrophages were noted surrounding and infiltrating the tumors, and a subset of these cells within the tumor appeared to be CD11d(+). Scattered macrophages at the tumor-brain interface were TLR4(+) and TLR9(+). Rare CD79a(+) B cells were noted in only a small subset of tumors. Lesser numbers of lymphocytes that were CD11d(+), CD45RA(+), or FoxP3(+) were noted in a number of the meningiomas. Although the function of these cells is not yet clear, work in other species suggests that evaluation of this immune cell infiltrate may provide important prognostic information and may be useful in the design of novel therapies.

The genetic features of 24 patients affected by familial and sporadic hemiplegic migraine.

Familial hemiplegic migraine (FHM) is the only migraine subtype for which a monogenic mode of inheritance, autosomal dominant has been clearly established. It is genetically heterogeneous and at least three different genes exist (CACNA1A, ATP1A2, and SCN1A), the so-called FHM1, FHM2, and FHM3 genes, respectively. Sporadic hemiplegic migraine (SHM) is a disorder, in which some patients may have their pathophysiology identical to FHM, but others, possibly the majority, may have different pathophysiology, probably related to the mechanisms of typical migraine with aura. In our study, we have screened the DNA of 24 patients affected by FHM and SHM. Only in three patients, 2 sporadic and 1 familial cases, we have described genetic mutations, all of them in the ATP1A2 gene. In our opinion, these results demonstrate a more frequent involvement of the ATP1A2 gene not only in the sporadic form, but probably also in the Italian FHM patients without permanent cerebellar signs. Moreover, the absence of CACNA1A, ATP1A2 and SCN1A mutations in the other 12 familial cases suggests the involvement of still unknown genes.

Effects on renal function of obstructive and nonobstructive dilatation of the upper urinary tract in ileal neobladders with refluxing ureteroenteric anastomoses.

AIMS: To investigate the incidence and long-term effects on kidney function of obstructive and nonobstructive dilatation of the upper urinary tract in patients with ileal neobladder with refluxing ureterointestinal anastomoses. METHODS: We retrospectively analyzed a prospectively derived database of 110 patients with bladder cancer and who were treated with an ileal neobladder between 1996 and 2007 using refluxing end-to-side ureterointestinal anastomoses on a short afferent limb. The mean follow up was 65 months. At every follow up visit the patients had an analysis of serum creatinine, urine culture, abdominal CT or ultrasonography, and, if there was dilatation of the upper urinary tract, 99mTc-DTPA renal scintigraphy was requested. RESULTS: In all, 206 renoureteral units were included in the study. Overall, seven had anastomotic stricture and of those, three were symptomatic and were corrected; while four were asymptomatic and of those, only two, with preserved split GFR, were surgically treated, while the remaining two, with a poor split GFR, were followed up. The last 99mTc-DTPA showed a preserved split GFR in the reimplanted units and further split renal function decrease in untreated units. Nonobstructive dilatation of the upper urinary tract, caused by reflux, was diagnosed in 13 units. The dilatation was bilateral in three patients with recurrent UTIs and urosepsis, and the split GFR was bilaterally reduced at diagnosis with a further reduction at the last 99mTc-DTPA. The remaining seven units with sterile urine, showed a preserved split GFR during follow up. CONCLUSIONS: All strictures, regardless of their severity, should be immediately corrected. Reflux per se does not provoke renal impairment unless recurrent UTIs and urosepsis are present.

DCUN1D1 is a risk factor for frontotemporal lobar degeneration.

BACKGROUND AND PURPOSE: Frontotemporal lobar degeneration (FTLD) is considered as a proteinopathy; therefore, it is conceivable that genes encoding for factors involved in protein misfolding and/or degradation could play a role in its pathogenesis. METHODS: An association study of defective in cullin neddylation 1 (DCN-1)-domain containing 1 (DCUN1D1), which is involved in protein degradation, was carried out in a population of 220 patients with FTLD as compared with 229 age-matched controls. RESULTS: A statistically significant increased frequency of the GG genotype of the DCUN1D1 rs4859146 single nucleotide polymorphism (SNP) was observed in patients compared with controls (6.9 vs. 1.7%, P = 0.011, adjusted OR: 4.39, 95% CI: 1.40-13.78). Stratifying according to the clinical syndrome, significant differences were observed between the behavioral variant of frontotemporal dementia and controls (GG frequency: 6.3 vs. 1.7%, P = 0.02, OR:4.0, 95%, CI = 1.24-12.92), as well as between patients with progressive aphasia compared with controls (15.4 vs. 1.7%, P = 0.014, OR = 11.30, 95%, CI = 1.63-78.45), but not in patients with SD versus controls (8.3 vs. 1.7%, P = 0.18, OR = 5.24, 95% C.I. = 0.45-60.63). No significant differences in allelic and genotypic frequencies of the DCUN1D1 rs4859147 SNP were found. CONCLUSIONS: The GG genotype of the DCUN1D1 rs4859147 SNP represents a risk factor for the development of FTLD, increasing the risk of about fourfold.

Glansectomy with split-thickness skin graft for the treatment of penile carcinoma.

Using our prospectively derived database, we identified 17 patients with squamous-cell carcinoma involving the glans penis, who were treated using organ-sparing surgery between March 2003 and January 2008. Of them, two were treated with partial glansectomy with primary glans closure, and 15 underwent total glans amputation and reconstruction of a new glans using a split-thickness skin graft (STSG). These 15 patients represent the subject of our study (mean age 51 years, range 42 to 59 years). Overall, two patients had early partial loss of the graft and of them, one required surgical regrafting. Two late complications occurred, consisting of one meatal stenosis and one postoperative phimosis. At a mean follow-up of 36 months, functional results were extremely satisfactory. All patients maintained their erectile function with good vaginal penetration starting from 3 months after surgery, with a range between 2 and 6 months. Orgasm and ejaculation were preserved in all patients, although reduced glans sensitivity was reported by all patients. No local recurrences were reported.

[Paraneoplastic syndromes: a review]. / Le sindromi paraneoplastiche: revisione critica della letteratura.

Modern oncology often obtains good results against earlier neoplasms, whilst it's still in difficulties against the advanced ones. The knowledge of paraneoplastic syndromes is crucial both to cure patients and to do an earlier diagnosis. When we recognize a paraneoplastic syndrome that comes before the clinic beginning of a neoplasm, perhaps we save a life. This review discusses all the main paraneoplastic syndromes, focusing mainly on their clinical aspect and reminding the most commonly associated cancers.

Brain flow changes before and after deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) markedly improves motor symptoms and reduces medication needs in Parkinson's disease (PD) patients. However, its effect on brain function has remained unclear. We used SPECT and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the STN in 22 PD patients and 13 healthy controls. PD patients were divided into good and poor responders to DBS, if changes in "off" UPDRS motor scores after surgery were >60% or <40%, respectively. Statistical analysis was performed using the SPM99 software. At baseline, all PD patients showed significant perfusion reductions in cortical areas (premotor frontal, parietal, and occipital). After DBS, changes were normalized only in the good responders, while cortical defects in the poor responders were unchanged. No flow decrements were detected in basal ganglia and thalamus in both groups, suggesting that DBS does not have a "lesion-like" effect. We conclude that good surgery outcome is associated with normalization of cortical flow abnormalities in PD.

Expression analysis of five tobacco EIN3 family members in relation to tissue-specific ethylene responses.

Ethylene induces different sets of genes in different tissues and at different stages of development. To investigate whether these differential responses are caused by differential expression of members of the EIN3 family transcription factors, five tobacco family members were isolated. They can be divided into three subgroups, which is probably due to the amphidiploid nature of tobacco. In phylogenetic analysis, each of the subgroups clustered with one of the three tomato EIL proteins and all NtEILs proved to be most homologous to Arabidopsis EIN3 and EIL1. Although organ-specific ethylene responses have been observed before, northern blot analysis showed that all NtEILs were expressed in all organs. To study differential NtEIL expression at the cellular level, in situ hybridization was used on the tobacco ovary. It was found that different ovary tissues displayed variable ethylene-induced expression of two ethylene-responsive marker genes. By contrast, no differences were found in expression level or tissue-specificity for any of the NtEILs in the ovary, before or after ethylene treatment. This indicates that the organ and tissue-specific ethylene responses are not caused by differential expression of NtEIL family members. These results support a model in which the developmental signals that regulate the tissue-specific responses are integrated with the ethylene signal downstream of a common primary ethylene-signalling pathway.

Functional neuroimaging (PET and SPECT) in the selection and assessment of patients with Parkinson's disease undergoing deep brain stimulation.

Deep brain Stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor complications who can no longer be improved by adjustment of medical therapy. Selection of surgery candidates and follow-up after surgery are critical for good outcome. Functional neuroimaging can help in the clinical assessment of these patients. We have used single photon emission computed tomography (SPECT) and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the subthalamic nucleus (STN) in 20 patients with advanced PD. We found a significant increase in the anterior cingulate/supplementary motor cortex in the 12 good responders (change in off unified UPDRS >50%). Conversely, patients with poor response (n=8; change in off UPDRS-III <50% following DBS) revealed a significant worsening of cortical hypoperfusion particularly in the prefrontal areas. No flow decrements were detected in the basal ganglia and in the thalamus in both groups during DBS stimulation suggesting that DBS does not have a "lesion like" effect. If DBS stimulates and does not inactivate STN projection neurons, flow reduction in the poor responders may be secondary to increased inhibitory basal ganglia output.

Ethylene regulates the timing of anther dehiscence in tobacco.

We investigated the involvement of ethylene signaling in the development of the reproductive structures in tobacco ( Nicotiana tabacum L.) by studying flowers that were insensitive to ethylene. Ethylene-insensitivity was generated either by expression of the mutant etr1-1 ethylene-receptor allele from Arabidopsis thaliana or by treatment with the ethylene-perception inhibitor 1-methylcyclopropene (MCP). Development of ovaries and ovules was unaffected by ethylene-insensitivity. Anther development was also unaffected, but the final event of dehiscence was delayed and was no longer synchronous with flower opening. We showed that in these anthers degeneration of the stomium cells and dehydration were delayed. In addition, we found that MCP-treatment of detached flowers and isolated, almost mature anthers delayed dehiscence whereas ethylene-treatment accelerated dehiscence. This indicated that ethylene has a direct effect on a process that takes place in the anthers just before dehiscence. Because a similar function has been described for jasmonic acid in Arabidopsis, we suggest that ethylene acts similarly to or perhaps even in concurrence with jasmonic acid as a signaling molecule controlling the processes that lead to anther dehiscence in tobacco.

Characterization and localization of the transmitting tissue-specific PELPIII proteins of Nicotiana tabacum.

The class III pistil-specific PELP proteins (PELPIII) of Nicotiana tabacum includes at least two members of highly soluble glycoproteins containing glucan modules that are characteristic for arabinogalactan proteins (AGPs). PELPIII accumulates in the style transmitting tissue (TT) during pistil development and, at flower anthesis, is present in the intercellular matrix (IM) of non-pollinated pistils. After pollination, PELPIII appears to be directly and completely translocated from the IM into the pollen tube callose walls, no significant accumulation was observed in the primary wall in the tip. In the spent parts of the pollen tubes these proteins become detectable against the remnants of the tube cell membrane and in the callose plugs. Different protein extraction procedures of PELPIII from pollinated tobacco pistils showed that these proteins remain in the highly soluble protein fraction and are not modified by the growing pollen tubes. These data concur with a role in IM development and pollen tube growth. In addition, the data show that the PELPIII are able to reach the cell membrane, facilitated by an already present or induced high porosity of the tube wall and an additional, yet unknown, mechanism. The differences in behaviour between the three related classes of style IM glycoproteins of Nicotiana, namely, PELPII, TTS and the 120 kDa glycoprotein, are proposed to connect more to their differences in glycosylation than to major differences in amino acid sequence.